We plan to review completely the medical records of all patients followed at the Moore Genetics Clinic for the Marfan syndrome in order to document the natural history of the clinical manifestations of this disorder. It may be possible to identify subpopulations of patients based on clinical presentation; this would lend support to the notion of genetic heterogeneity as well as enable more enlightened medical management. This proposal also concentrates on the cardiovascular changes in the Marfan syndrome, particularly aortic dilation, the clinical complication which accounts for much morbidity and most of the early patient mortality seen in this syndrome. In an attempt to retard or prevent further aortic dilatation, propranolol, a beta-adrenergic blocking agent, will be given to all Marfan patients with aortic regurgitation; patients who only have enlarged aortas will be randomly assigned to propranolol therapy or to no pharmacologic therapy. Aortic dilation will be measured serially by one- and two-dimensional echocardiography. Propranolol dosage will be monitored by serum levels, systolic time intervals and ventricular and aortic wall velocity to optimize the negative inotropic effect. Studies of the adverse reactions to propranolol will be conducted by recording serial pulmonary function tests, psychological profiles, and electroencephalograms. The potential significance of these studies includes: delaying the occurrence of the main life-threatening sequelae of the Marfan syndrome; documenting the natural history of the mitral valve, aortic valve, and aortic root lesions by a new and more sensitive echocardiographic method; understanding the pulmonary and nervous system side effects of propranolol; and, greatly expanding the recorded experience regarding the clinical manifestations, genetics and heterogeneity of the Marfan syndrome.